An overview of the tumor microenvironment, from cells to complex networks (Review)

Abstract

For a long period, cancer has been believed to be a gene disease, in which oncogenic and suppressor mutations accumulate gradually, finally leading to the malignant transformation of cells. This vision has changed in the last few years, the involvement of the tumor microenvironment, the non-malignant part of the tumors, as an important contributor to the malignant growth being now largely recognized. There is a consensus according to which the understanding of the tumor microenvironment is important as a means to develop new approaches in the therapy of cancer. In this context, the present study is a review of the different types of non-malignant cells that can be found in tumors, with their pro or antitumoral actions, pre sence in tumors and therapeutic targeting. These cells establish complex relations between them, through cytokines, exosomes, cell adhesion, co-stimulation and co-inhibition; these relations will also be examined in the present work. Contents 1. Introduction 2. Cellular participants to the tumor microenvironment 3. The tumor microenvironment, from biogenesis to complex relations 4. Conclusions and perspectives

Optimizing NK Cell-Based Immunotherapy in Myeloid Leukemia: Abrogating an Immunosuppressive Microenvironment

“…The TME is a major impediment in enhancing the anti-tumor effects of NK cells. As a complex network, it comprises TAMs, MDSCs, Tregs, regulatory gdT cells, soluble factors, the extracellular matrix, and suppressive molecules expressed on tumor cells (24,(98)(99)(100)(101). Tumor cells evade immune escape by establishing an immunosuppressive microenvironment, promoting tumor progression and metastasis (102).…”

To inhibit or to boost the ATP/P2RX7 pathway to fight cancer—that is the question

“…It is now well documented that vascular networks and supporting cells are required to ensure the expansion of healthy tissues as well as the growth of tumors [2]. Thus, in addition to directly target tumor cells, the non-cancerous cells present in the tumor microenvironment (TME) can also be viewed as relevant targets, even if this domain is now more and more complex [3].…”

Structure vs. Function of TRIB1—Myeloid Neoplasms and Beyond

“…The tumour microenvironment is fundamental to the development, progression and drug response of tumours and is regulated by a number of factors, including the excretion of cytokines by tumour cells [ 74 , 75 ]. In prostate cancer, the overexpression of TRIB1 promotes cytokine secretion from the tumour cells, which drives the polarisation of M2-like tissue-resident macrophages in the tumour microenvironment [ 62 ].…”

“…In prostate cancer, the overexpression of TRIB1 promotes cytokine secretion from the tumour cells, which drives the polarisation of M2-like tissue-resident macrophages in the tumour microenvironment [ 62 ]. M2-like macrophages are important protumour, anti-inflammatory macrophages that can suppress the local immune response and promote tumour growth [ 62 , 74 , 75 ]. TRIB1 overexpression promotes the secretion of IL8 and CXCL2, among other cytokines, from prostate cancer cells by inhibiting the NF-κB inhibitor IKB-zeta [ 62 ].…”